Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors ...Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.展开更多
Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ...Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model.All rats were divided into 4 groups:the control group,the chitinase group,the HCC group,and the HCC+chitinase group.The antiproliferative effect of chitinase was evaluated in human HCC cells.The effect of chitinase in vivo on oxidative stress,endoplasmic reticulum stress chaperones,autophagy markers,PI3K/AKT/mTOR,AMPK pathway expression,and apoptotic indicators was determined and confirmed by histological examination.Results:Chitinase significantly inhibited the viabilities of HepG2 cells.Moreover,in the Wistar male rat model of HCC,chitinase decreased ATP levels,modulated endoplasmic reticulum stress,mediated autophagy factors,and promoted apoptosis.Conclusions:Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.展开更多
基金supported by the National Natural Science Foundation of China to L.H.(32470754 and 32070750)to X.M.(32170824 and 32322027)HRHl program of Westlake Laboratory of Life Sciences and Biomedicine to X.M.(1011103360222B1).
文摘Potassium channels regulate diverse biological processes,ranging from cell proliferation to immune responses.However,the functions of potassium homeostasis and its regulatory mechanisms in adult stem cells and tumors remain poorly characterized.Here,we identify Sandman(Sand),a two-pore-domain potassium channel in Drosophila melanogaster,as an essential regulator for the proliferation of intestinal stem cells and malignant tumors,while dispensable for the normal development processes.Mechanistically,loss of sand elevates intracellular K+concentration,leading to growth inhibition.This phenotype is rescued by pharmacological reduction of intracellular K+levels using the K+ionophore.Conversely,overexpression of sand triggers stem cell death in most regions of the midgut,inhibits tumor growth,and induces a Notch loss-of-function phenotype in the posterior midgut.These effects are mediated predominantly via the induction of endoplasmic reticulum(ER)stress,as demonstrated by the complete rescue of phenotypes through the co-expression of Ire1 or Xbp1s.Additionally,human homologues of Sand demonstrated similar ER stress-inducing capabilities,suggesting an evolutionarily conserved relationship between this channel and ER stress.Together,our findings identify Sand as a shared regulatory node that governs Drosophila adult stem cell dynamics and tumorigenesis through bioelectric homeostasis,and reveal a link between the two-pore potassium channel and ER stress signaling.
文摘Objective:To assess the antitumor activity of the novel chitinase produced by fermented,isolated Trichoderma viride in a hepatocellular carcinoma(HCC)male rat model.Methods:Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model.All rats were divided into 4 groups:the control group,the chitinase group,the HCC group,and the HCC+chitinase group.The antiproliferative effect of chitinase was evaluated in human HCC cells.The effect of chitinase in vivo on oxidative stress,endoplasmic reticulum stress chaperones,autophagy markers,PI3K/AKT/mTOR,AMPK pathway expression,and apoptotic indicators was determined and confirmed by histological examination.Results:Chitinase significantly inhibited the viabilities of HepG2 cells.Moreover,in the Wistar male rat model of HCC,chitinase decreased ATP levels,modulated endoplasmic reticulum stress,mediated autophagy factors,and promoted apoptosis.Conclusions:Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.
